Biomedical subjects

Dongfang Wang

Publications and source records attributed to Dongfang Wang.

17 recordsLinked to original sources

PubMed2006

Partially redundant functions of two SET-domain polycomb-group proteins in controlling initiation of seed development in Arabidopsis.

In Arabidopsis, a complex of Polycomb-group (PcG) proteins functions in the female gametophyte to control the initiation of seed development. Mutations in the PcG genes, including MEDEA (MEA) and FERTILIZATION-INDEPENDENT SEED 2 (FIS2), produce autonomous seeds where endosperm proliferation occurs in the absence of fertilization. By using a yeast two-hybrid screen, we identified MEA and a related protein, SWINGER (SWN), as SET-domain partners of FIS2. Localization data indicated that all three proteins are present in the female gametophyte. Although single-mutant swn plants did not show any defects, swn mutations enhanced the mea mutant phenotype in producing autonomous seeds. Thus, MEA and SWN perform partially redundant functions in controlling the initiation of endosperm development before fertilization in Arabidopsis.

Arabidopsis↗

PubMed2006

Hemodynamic analysis and design of a paracorporeal artificial lung device.

We have extended our model of the ovine pulmonary circulation to include a model of a paracorporeal artificial lung (AL) and its attachments to the natural pulmonary circulation in two configurations: in series and in parallel. Our model of the natural lung (NL) circulation is first shown to be in agreement with hemodynamic and input impedance data from the open literature. We then study design efficacy of the AL in terms of its housing and attachments. A sensitivity analysis of the modified pulmonary circulation model reveals that there are three key parameters: inlet graft length (IGL) and the compliances of the inlet compliance chamber (CC) and housing of the artificial lung. Based on literature reports, we assume the right ventricle is well-matched to the impedance of the natural pulmonary circulation and adjust the parameters of the modeled AL circuit to achieve the best least-squares fit to natural pulmonary input impedance data. Best-fit parameters produce impedance curves that fit natural impedance well, particularly below 3 Hz, where both compliance and graft length have their largest effects. Of these parameters, the impedance profile is most sensitive to IGL. However, the compliances are important, as well, particularly at low frequencies.

Animals↗

PubMed2005

Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in vitro.

PURPOSE: We sought to determine whether hypoxia-induced radioresistance is mediated by the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha). METHODS AND MATERIALS: We used 2 mouse embryonic fibroblast cell lines transformed with H-ras and TAg, 1 HIF-1alpha+/+ and the other HIF-1alpha-/-. Cell were exposed to either 95% air and 5% CO2 (normoxic conditions) or 0.2% O2, 94.8% N2, and 5% CO2 (hypoxic conditions) for 4 hours. Cells were then irradiated and subjected to clonogenic survival assays. RESULTS: Whereas neither +/+ ras/TAg nor -/- ras/TAg cells expressed HIF-1alpha under normoxic conditions, hypoxia induced expression of HIF-1alpha only in +/+ ras/TAg cells, confirming the absence of HIF-1alpha in -/- ras/TAg cells. Clonogenic survival curves for +/+ ras/TAg and -/- ras/TAg cells under normoxia and hypoxia demonstrated that hypoxia increased radioresistance in both cell lines to the same degree. At 1-log cell kill, the +/+ ras/TAg and -/- ras/TAg cells had an identical oxygen enhancement ratio of 1.28 +/- 0.09 and nearly identical oxygen enhancement ratios at 2-log cell kill. CONCLUSION: In our system of transformed mouse embryonic fibroblasts, hypoxia-mediated radiation resistance is independent of HIF-1alpha.

Animals↗

PubMed2005

Development of a hypoxia-inducible cytosine deaminase expression vector for gene-directed prodrug cancer therapy.

One important feature of human solid tumors is the presence of a hypoxic microenvironment. Under hypoxia, genes that contain a hypoxia-response element (HRE) can be activated by the binding of hypoxia-inducible factor-1. To reach the goal of selectively killing tumor cells in a hypoxic microenvironment using a gene therapy approach, we developed a cytosine deaminase (CD) gene construct (pH9YCD2) that contains an HRE gene enhancer. CD is an enzyme that catalyzes the conversion of noncytotoxic 5-fluorocytosine (5-FC) to the cytotoxic and radiosensitizing drug 5-fluorouracil (5-FU). Yeast CD was cloned into an SV40 promoter-based mammalian expression vector, and an HRE enhancer was inserted in front of the promoter. Human glioblastoma U-87 MG cells were transfected with pH9YCD2. Western blots revealed that CD was strongly expressed under hypoxic conditions (0.3-1% O2), whereas only minor CD expression was seen under normoxic conditions. To confirm that the expressed CD enzyme retains catalytic activity, we performed a 5-FC/5-FU-conversion assay in which 5-FC was incubated with the lysates of pH9YCD2-transfected cells. The percentage of conversion from 5-FC to 5-FU was 63% under hypoxia versus 13% under normoxia. In vitro, cell viability and colony-forming efficiency assays demonstrated that the gene construct was able to significantly kill glioblastoma cells in a hypoxia-dependent manner. In addition, 5-FC treatment of hypoxic pH9YCD2-transfected cells produced a marked bystander effect, which could be a distinct advantage for gene therapy. If this construct exhibits antitumor efficacy in vivo, it may have promise as an antitumor agent in humans.

Blotting, Western↗

PubMed2005

Seventy-two hour gas exchange performance and hemodynamic properties of NOVALUNG iLA as a gas exchanger for arteriovenous carbon dioxide removal.

OBJECTIVE: Acute respiratory failure is complicated by acidosis and altered end-organ perfusion. NOVA-LUNG iLA is an interventional lung assist (ILA) device for arteriovenous carbon dioxide removal (AVCO2R). The present study was conducted to evaluate the device for short-term CO2 removal performance and hemodynamic response. METHODS: Six adult sheep received cannulation of the jugular vein and carotid artery. The ILA-AVCO2R circuit was placed on the sheep for 72 hours. Hemodynamics and PaCO2 were measured; CO2 removal was calculated while varying sweep gas flow rates (Qg), device blood flow rates (Qb), and PaCO2. RESULTS: Hemodynamic variables remained normal throughout the 72 hour study. CO2 removal increased with increases in Qg or Qb. Mean CO2 removal was 119.3 ml/min for Qb 1 L/ min, Qg 5 L/min, and PaCO2 40-50 mmHg. PaCO2 was directly proportional to CO2 clearance (R=0.72, p <0.001). CONCLUSION: NOVALUNG iLA can provide near total CO2 removal with Qb 1-2 L/min, Qg 5 L/min, and minimal flow resistance (3.88+/-0.82 mmHg/L/min). PaCO2 correlates with CO2 removal and is dependent on Qb and Qg.

Animals↗

PubMed2004

St Thomas Hospital Cardioplegia #2 fails to suppress slow reaction pacemaker cell electrical activity.

BACKGROUND: Inadequate right atrial myocardial preservation during cardioplegic arrest may promote postoperative supraventricular arrhythmias (SVA). We determined (1). if oxygenated St. Thomas Hospital Cardioplegia #2 (STH2) alone causes slow reaction pacemaker cell (SR) quiescence; and (2). if hypothermia, higher [K(+)], lower [Ca(2+)], and verapamil in STH2 suppresses SR electrical activity. MATERIALS AND METHODS: A glass microelectrode recorded SA node SR membrane action potentials (AP) in rabbits (n = 23, 1.93 +/- 0.45 kg) randomized to normothermic STH2 (33 degrees C, n = 6), hypothermia (20 degrees C, n = 4), hypothermic STH2 (22 degrees C, n = 3), lower calcium STH2 (n = 3), higher potassium STH2 (n = 4), and STH2 plus Verapamil (n = 3). RESULTS: Normothermic STH2 depressed SR action potential amplitude and action potential duration (APD), but did not completely suppress action potential generation. Hypothermia alone prolonged APD and sinus cycle length and suppressed SR AP. STH2 with hypothermia (to 20 degrees C) completely suppressed propagating AP and STH2 plus 0.04 Ca(2+) mEq/L inhibited SR AP generation. STH2 plus 30 mEq K(+) and STH2 plus 2.5 mmol/L verapamil failed to generate SR AP. CONCLUSION: STH2 cannot prevent SA node SR myocardial cells from low-amplitude AP autogeneration above 21 degrees C. STH2 with 30 mEq/L K(+), STH2 with 0.02 mEq/L Ca(2+), and STH2 plus 2.5 mmol/L verapamil can arrest AP generation in SR and potentially prevent postoperative SVA.

Animals↗

PubMed2003

Heat sensitivity in a bentgrass variant. Failure to accumulate a chloroplast heat shock protein isoform implicated in heat tolerance.

Two variants of creeping bentgrass (Agrostis stolonifera cv palustris), developed using tissue culture, have been used to determine the roles of chloroplast-localized small heat shock proteins (CP-sHSPs) in heat tolerance. Results from previous research indicate that the heat-tolerant variant expressed two additional CP-sHSP isoforms not expressed in the heat-sensitive variant, that accumulation of the additional CP-sHSP isoforms was genetically linked to thermotolerance, and that the presence of the additional isoforms in the heat-tolerant variant provided greater protection to photosystem II during heat stress. To determine the basis of the differential expression, we isolated the genes encoding the CP-sHSPs from both variants and characterized their structure and expression. Two genes, ApHsp26.2 and ApHsp26.7a, were isolated from the heat-tolerant variant, and three genes, ApHsp26.2m, ApHsp26.8, and ApHsp26.7b, were isolated from the heat-sensitive variant. The sequence of ApHsp26.2m from the heat-sensitive variant was identical to ApHsp26.2, except for a point mutation that generated a premature stop codon. Therefore, the protein product of ApHsp26.2m did not accumulate in the heat-sensitive line. Mass spectrometry analysis confirmed that ApHsp26.2 encoded for the CP-sHSP isoforms unique to the heat-tolerant variant. An identical mutation was detected in one of the three parental lines used to develop the creeping bentgrass variants. This suggests that ApHsp26.2m was inherited from this parent and did not arise from a mutation that occurred during tissue culture. The presence of two isoforms encoded by the same gene might be due to differential processing of the N-terminal amino acids during or after import into the chloroplast.

Adaptation, Physiological↗

PubMed2002

The paracorporeal artificial lung improves 5-day outcomes from lethal smoke/burn-induced acute respiratory distress syndrome in sheep.

BACKGROUND: Our low-impedence, paracorporeal artificial lung (PAL) prototype is well-tolerated in-series with the normal sheep pulmonary circulation. Using our lethal dose 80% to 100% smoke/burn acute respiratory distress syndrome (ARDS) sheep model, we compared PAL to volume-controlled mechanical ventilation (VCMV) in a prospective, randomized, controlled, unblinded, 5-day outcome study. METHODS: Fourteen sheep were randomized to PAL (n = 8) versus VCMV (n = 6) to assess outcome. For PAL, arterial cannulas were anastomosed to the proximal and distal main pulmonary artery with an interposing snare diverting full flow through a paracorporeal loop. Acute respiratory distress syndrome was induced in both groups (48 breaths smoke insufflation, third degree burn on 40% of total body surface area). When acute respiratory distress syndrome criteria were met (24 to 30 hours after injury), the PAL was interposed in the paracorporeal loop. Both groups were managed with a VCMV algorithm minimizing tidal volume, ventilator rate, and fractional inspired concentration of oxygen (FiO2). RESULTS: Six of eight PAL versus 1 of 6 VCMV sheep survived the 5-day study. In PAL, cardiac output, mean arterial pressure, pulmonary artery pressure, left atrial pressure, and central venous pressure remained stable. Average PAL gas transfer was 218.6 +/- 17.7 mL/min O2 and 183.0 +/- 27.8 mL/min CO2. Ventilator settings 48 hours after lung injury in PAL were significantly lower (p < 0.05) than VCMV (TV 210 versus 425 mL; respiratory rate 6 versus 29 breaths/min; minute ventilation 1.2 versus 10.8 L/min; FiO2 21 versus 100%). Likewise, PaO2/FiO2 ratio was normalized in PAL and still met acute respiratory distress syndrome criteria in VCMV. The PAL wet/dry ratio was significantly lower than VCMV (6.36 +/- 0.63 versus 11.85 +/- 1.54; p = 0.008). CONCLUSIONS: In a prospective, randomized, controlled, unblinded, outcomes study, PAL decreased ventilator-induced lung injury in a lethal dose 80% to 100% ARDS model to improve 5-day survival.

Animals↗

PubMed2002

Expression and endocytosis of VEGF and its receptors in human colonic vascular endothelial cells.

Normal human colonic microvascular endothelial cells (HUCMEC) have been isolated from surgical specimens by their adherence to Ulex europaeus agglutinin bound to magnetic dynabeads that bind alpha-L-fucosyl residues on the endothelial cell membrane. Immunocytochemistry demonstrated the presence of a range of endothelial-specific markers on HUCMEC, including the von Willebrand factor, Ulex europaeus agglutinin, and platelet endothelial cell adhesion molecule-1. The growing cells form monolayers with the characteristic cobblestone morphology of endothelial cells and eventually form tube-like structures. HUCMEC produce vascular endothelial growth factor (VEGF) and express the receptors, kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase, through which VEGF mediates its actions in the endothelium. VEGF induces the tyrosine phosphorylation of KDR and a proliferative response from HUCMEC comparable to that elicited from human umbilical vein endothelial cells (HUVEC). On binding to HUCMEC or HUVEC, (125)I-labeled VEGF internalizes or dissociates to the medium. Once internalized, (125)I-labeled VEGF is degraded and no evidence of ligand recycling was observed. However, significantly less VEGF is internalized, and more is released to the medium from HUCMEC than HUVEC. Angiogenesis results from the proliferation and migration of microvascular, not large-vessel, endothelial cells. The demonstration that microvascular endothelial cells degrade less and release more VEGF to the medium than large-vessel endothelial cells identifies a mechanism permissive of the role of microvascular cells in angiogenesis.

Autocrine Communication↗

PubMedDate not supplied

Percutaneous retrieval of chronic intravascular foreign bodies.

To evaluate the feasibility of intravascular retrieval of chronic foreign bodies, we retrospectively reviewed an 8 year experience (1993-2001) of percutaneous retrieval of chronically retained intravascular foreign bodies (n = 6). In 6 of 6 cases (4 catheter fragments, 2 guidewires), 5-90 days elapsed before retrieval via the femoral or internal jugular vein. Under fluoroscopy, we determined the foreign body's course, position and size. A guidewire was advanced through a multipurpose catheter to the foreign body. The multipurpose catheter was replaced with a gooseneck snare catheter and the snare advanced to grasp and remove the foreign body. Percutaneous retrieval was successful in all 6 cases. One patient experienced mild hemoptysis, which resolved within 24 hr of observation. No patient experienced long-term sequelae. Given the potential life-threatening complications from intravascular foreign bodies and the low complication rate from percutaneous retrieval, we recommend extraction of the foreign body even if it is asymptomatic in the chronic setting (> 24 hr).

Adolescent↗

PubMedDate not supplied

The effect of augmented hemodynamics on blood flow during arteriovenous carbon dioxide removal.

Arteriovenous carbon dioxide removal (AVCO2R) as an alternative treatment for acute respiratory distress syndrome uses a low resistance gas exchanger in a simple arteriovenous shunt to achieve total CO2 removal and allow lung rest. We have previously shown in our clinically relevant LD40 ovine model of smoke/burn induced acute respiratory distress syndrome that AVCO2R allows significant decreases in respiratory rate, tidal volume, peak airway pressure, and FiO2, as compared with standard mechanical ventilation. In addition, we have shown in a prospective randomized outcomes study that AVCO2R increases ventilator free days, decreases ventilator dependent days, and significantly improves survival. The purpose of this study is to further define the limits of AVCO2R through hemodynamic augmentation and evaluation of peak end expiratory pressure (PEEP). Administration of an alpha agonist (phenylephrine) and a beta agonist (isoproterenol) increased mean arterial pressure (MAP) and cardiac output (CO), respectively. MAP increases ranged from 2.4% to 94.4% and CO increases ranged from 33% to 146%. Phenylephrine caused elevations in MAP (2.4-94.4%) and AVCO2R flow (9-67%), and CO never decreased more than 10%. Isoproterenol administration increased CO (33-146%), decreased MAP (9-54%), and decreased AVCO2R flow (11-42%). In a second group, PEEP was increased stepwise from 0 (baseline) to 20 cm H2O. Increasing PEEP did not result in significant hemodynamic changes (< 10% change from baseline PEEP) for MAP, CO, or AVCO2R flow. In conclusion, alpha agonist administration increased AVCO2R blood flow, whereas beta agonist administration decreased MAP and AVCO2R blood flow, despite CO elevation. Various levels of PEEP are well tolerated and thus allow a range of options during AVCO2R.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

High-frequency percussive ventilation with systemic heparin improves short-term survival in a LD100 sheep model of acute respiratory distress syndrome.

We undertook an assessment of high-frequency percussive ventilation (HFPV) and systemic heparin on survival in our LD100 sheep model of smoke/burn-induced acute respiratory distress syndrome (ARDS). This was a prospective controlled outcomes study in a large animal critical care laboratory. ARDS was induced in 13 sheep by a combination of 48 cotton smoke breaths and 40% full-thickness cutaneous burn (LD100) followed by mechanical ventilation (15 ml/kg tidal volume). After meeting ARDS criteria (PaO2/FiO2 < 200), the sheep were divided into high-frequency percussive ventilation (HFPV; n = 7) or volume-controlled mechanical ventilation (VCMV; n = 6) groups. Both groups received systemic heparin to achieve an ACT 180-300 seconds. HFPV was managed with the Volumetric Diffusive Respiration Ventilator (Percussionaire Corp., Sandpoint, ID). The VCMV group was managed with up to 10 ml/kg tidal volume. Arterial blood gases and ventilator settings were monitored every 6 hours after onset of ARDS. HFPV did not affect sheep hemodynamics. Survival 84 hours after smoke and burn injury was significantly greater in the HFPV (7/7, 100%) compared with the VCMV group (3/6, 50%, P < .05). PaCO2 was significantly greater in VCMV group at 36, 48, and 72 hours after smoke and burn injury. PaO2/FiO2 after 36 hours of smoke and burn injury in the HFPV group was improved compared with the VCMV group, but no statistical difference was found. In the VCMV group, peak airway pressure was decreased to 19.7 +/- 2.2 cm H2O at 36 hours from 29 +/- 2.8 at 24 hours as the tidal volume changed from 15 ml/kg to 10 ml/kg and then gradually increased to 39 +/- 5.6 cm H2O at 72 hours. In the HFPV group, peak inspiratory pressure kept constant at a level of 30 cmH2O. In our smoke/burn-induced LD100 sheep model of ARDS, volume-controlled mechanical ventilation with systemic heparin achieved a 50% survival whereas HFPV with systemic heparin achieved 100% survival at 60 hours after the onset of ARDS.

Animals↗

PubMedDate not supplied

Toward ambulatory arteriovenous CO2 removal: initial studies and prototype development.

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100-150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500-900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 +/- 0.8 mm Hg, and mean CO2 removal was 104.8 +/- 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.

Animals↗

PubMedDate not supplied

Short term performance evaluation of a perfluorocopolymer coated gas exchanger for arteriovenous CO2 removal.

A new perfluorocopolymer coating for micropore hollow fiber gas exchangers was developed to improve gas exchange, reduce plasma leakage, and reduce blood-surface interactions. The present authors evaluated gas exchanger performance using this new coating in a prospective, randomized, controlled, unblinded, large animal model of CO2 retention. Adult sheep (30-40 kg), under general anesthesia, underwent cannulation of the carotid artery (12 F) and jugular vein (14 F). The perfluorocopolymer coated (n = 5) and uncoated (n = 5) gas exchangers were attached to an arteriovenous CO2 removal (AVCO2R) circuit. Blood gases, CO2 removal, and hemodynamics were monitored throughout the 6 hour study. Average CO2 removal was 107.6 +/- 15.6 ml/min (coated) vs. 93.0 +/- 13.9 ml/min (uncoated; p < 0.01). PaCO2 and CO2 removal for both coated and uncoated did not deteriorate significantly over the study. Average AVCO2R blood flow was 1,130 +/- 25 ml/min (coated) versus 1,101 +/- 79 ml/min (uncoated; p = not significant). Likewise, cardiac output and AVCO2R blood flow did not change over the duration of the study. No significant differences in the pressure gradient or resistance between devices (coated, 6.89 +/- 1.14 mm Hg/L/min; uncoated, 6.42 +/- 0.23 mm Hg/L/min) was noted. The authors concluded that the new perfluorocopolymer coated gas exchanger improved CO2 removal without compromising hemodynamics in an acute performance evaluation.

Animals↗

PubMedDate not supplied

Development of ambulatory arterio-venous carbon dioxide removal (AVCO2R): the downsized gas exchanger prototype for ambulation removes enough CO2 with low blood resistance.

We are developing an ultra compact gas exchanger to allow ambulation during arterial-venous CO2 removal (AVCO2R). The ambulatory AVCO2R gas exchanger (135 ml prime volume and 1.3 M2 gas exchange surface area) is made of polymethylpentene hollow fibers. The gas exchanger was attached to sheep carotid artery (12F) and jugular vein (14F) by percutaneous cannulae for 6 hours (n = 5). Device CO2 removal was measured and calculated at a constant blood flow rate of 1 L/min coupled with varying sweep gas from 1 to 15 L/min, and at constant sweep gas flow of 2 L/min coupled with varying blood flow from 0.5 to 1.25 L/min to determine capacity of CO2 removal at Pa CO2 = 40-50 mm Hg. Blood gases, CO2 removal and hemodynamics were recorded at 0, 3, and 6 hours. CO2 removal increased with sweep gas flow rate and with increase of device blood flow. Hemodynamics remained unchanged throughout study. Gas exchanger resistance remained stable at 2.3 +/- 0.53 mm Hg/L/min. CO2 removal with 1 L/min blood flow and 2 L/min sweep gas was 110 +/- 12 then stabilized at 85 +/- 14 mL/min to 6 hours. The compact ambulatory AVCO2R gas exchanger achieves stable, near total CO2 removal for at least 6 hours with a simple arteriovenous shunt.

Animals↗

PubMedDate not supplied

Use of aortic valvo-pumps placed in valve annulus for long-term left ventricular assist.

To provide better anatomical fit and physiologic adaptation, three aortic valvo-pumps with different dimensions were developed. Each pump has a rotor with an impeller and drive magnets and a stator consisting of a motor coil with iron core and an outflow guide vane. The devices had outer diameters of 21 mm, 23 mm, and 25 mm, respectively, and weighted 27 g, 31 g, and 40 g, respectively. Laboratory testing demonstrated that the rotating speed for maintaining a diastolic pressure of 80 mm Hg at zero flow rate should be 17500 rpm, 15000 rpm, and 12500 rpm, respectively; the largest flow at these same speeds will be 5 l/min, 7 l/min, and 10 l/min, respectively, with approximately 50 mm Hg pressure head increase. Therefore, these three pumps may meet the hemodynamic requirements of patients with body weights of 40-60 kg, 60-80 kg, and 80-100 kg. The first in vivo trial exhibited that the 25 mm valvo-pump can be sewn onto the aortic valve annulus of a 80 kg body weight pig without harm to adjacent organ functions. The devices occupy no additional anatomic space and deliver the blood directly from ventricle to the aorta, thus producing less physiologic disturbance to the natural circulation. Neither connecting conduits nor bypass circuits are necessary, thus eliminating the most dangerous sites of thrombosis in traditional left ventricular assist devices.

Animals↗

PubMedDate not supplied

Paracorporeal artificial lung: perioperative management for survival study in sheep.

An artificial lung may offer a bridge to recovery or transplant. Utilizing our recently developed paracorporeal artificial lung (PAL) in survival studies in sheep, we critically review our perioperative/anesthetic protocol. Adult Suffolk ewes (n = 15) underwent general anesthesia induced by ketamine (7-15 mg/kg, im) and isoflurane by mask, then intubated and maintained by 4.0-5.0% isoflurane titrated to mean arterial pressure (MAP) 70-110 mm Hg. After a latissimus-sparing thoracotomy and systemic heparinization (200 IU/kg), arterial grafts were anastomosed to the proximal and distal main pulmonary artery in an end-of-graft to side-of-artery fashion. A snare was passed around the pulmonary artery between anastomoses. When the snare was tightened, full pulmonary blood flow was diverted through the cannulae and immediately through the PAL. Perioperative crystalloids included a 500-mL prime, lactated Ringer's (LR) titrated to CVP 5-7 mm Hg, and a heparin infusion (activated clotting time [ACT] 250-300 s). Buprenorphine (0.3 mg im tid) controlled postoperative pain. Hemodynamic parameters, arterial blood gases (ABGs), and ACTs were measured every 6 h. Thirteen of 15 sheep survived the operation and were extubated in less than 20 min. Two groups were studied for up to 7-day survival. Both groups underwent immediate connection to the PAL diverting full pulmonary blood flow. Group 1 (n = 8) underwent immediate connection to a rigidly housed PAL, and 4 of 8 demonstrated immediate right heart failure. In Group 2 a compliance chamber was added to the PAL inflow, and 6 of 7 had stable hemodynamic function for the duration of the study. Incremental improvements in the PAL and our anesthetic and perioperative care have resulted in reliable survival in adult sheep allowing for artificial lung development.

Algorithms↗